These experiments have two broad objectives. First, we intend to localize and characterize the brain sodium-receptor mechanisms involved in the central induction of changes in renal sodium excretion (UNaV) and renin secretion secondary to alteration of CSF sodium. Experiments will continue to be carried out in dogs (anesthetized) and on unanesthetized rats. The CNS mechanism of response to changes in brain sodium will continue to be evaluated using: 1) ventriculocisternal perfusion, 2) localized push-pull perfusion in brain tissue and in ventricles, and 3) slow ventricular infusions in conscious rats. Our previous work on hypothalamic DI rats suggested that ADH was the likely mediator of the natriuresis, however, our latest work shows that a low constant infusion of ADH restores the response of the DI rats; therefore, in rats, a rise in ADH is not the sole cause of the natriuresis. However, preliminary dose-response studies in anesthesized dogs, comparing the natriuresis to similar plasma ADH (measured by RIA) achieved by exogeneous ADH or stimulation of the Na receptors with hi-(Na), contradict the rat-finding; so far (experiments in progress) there is a similar ADH/nutriuresis dose/response, regardless of the source of the ADH. Thus, in dogs, ADH does appear to be a major part of the efferent pathway. This coming year we will especially focus on chemical stimulation of the receptors. We will perfuse drugs which affect brain Na/K ATPase and/or intracellular (Na), to test the hypothesis that the receptor is activated by changes in membrane ATPase. An effective chemical stimulant will prove most helpful in localizing the site of stimulus activation via localized push-pull perfusions; the localization will also be confirmed by ablation of hypothetical receptor locations.